Essential Cell Biology 5th edition

Exploring Human Genetics
681
remainder of this chapter, we explore the genetic underpinnings of disease,
and the approaches that investigators use to identify them.
Many Severe, Rare Human Diseases Are Caused by
Mutations in Single Genes
About 3000 human diseases are caused by mutations in single genes.
These single-gene, or monogenic, disorders are sometimes referred to as
Mendelian because they show a pattern of inheritance that is as simple to
trace as that of the wrinkled peas and purple flowers that Mendel studied.
Most of these mutations are recessive; individuals who carry only one
copy of the mutant allele are largely asymptomatic, while those homozygous
for the mutation are severely impaired. For example, individuals
with Tay-Sachs disease, which is characterized by seizures, blindness,
and neurodegeneration, usually do not survive infancy.
Monogenic disorders also tend to be very rare, affecting only a fraction
of one percent of the human population. This low prevalence can be
attributed to a number of factors. First, many of these diseases are “early
onset,” meaning that affected individuals die early in life, often before
reproducing. The disease-causing alleles carried by these individuals are
thus eliminated from the gene pool. At the same time, because many
monogenic disorders are recessive, heterozygous individuals typically
lead normal lives and show no signs of the disease. Thus, the diseasecausing
alleles are never entirely eradicated from the population, and
instead persist at a low frequency. The disease then manifests itself only
in those rare individuals who inherit two mutant alleles. Monogenic disorders
can occur more frequently, however, in families or populations
in which the parents are genetically related. Such consanguineous marriages
are more likely to produce offspring that are homozygous for the
mutant, disease-causing alleles than are marriages between unrelated
individuals (Figure 19−36).
(A) incidence of birth defects (percentage)
key
4.0–4.9
5.0–5.4
5.5–5.9
6.0–6.4
6.5–6.9
7.0–7.9
8.0–8.2
key
0–4
5–9
20–29
30–39
40–49
50–59
60–69
(B) prevalence of consanguinity (percentage of total marriages between second cousins or closer)
Figure 19−36 The prevalence of
consanguineous marriage can
increase the likelihood of inheriting
disease-causing alleles. A comparison
of these two maps indicates the
large degree of overlap between
the percentage of consanguineous
marriages and the incidence of birth
defects in countries around the
world. (A) The percentage of birth
defects is indicated by blue shading.
Here, a birth defect is defined as any
abnormality affecting body structure
or function that is present from birth.
These include conditions caused by
simple, monogenic diseases, as well as
environmental factors, such as exposure
to chemicals that cause mutations.
(B) The proportion of marriages
between second cousins or closer is
indicated in orange. Gray shading
indicates countries for which data were
not available. (Adapted from M.A.
Jobling et al., Human Evolutionary
Genetics, 2nd ed. New York: Garland
Science, 2014. With permission from
Garland Science.)